Association between Nephrolithiasis and Kidney Disease Progression in Patients with Autosomal Dominant Polycystic Kidney Disease from a Single-Center, Prospective Cohort

Background: Nephrolithiasis is a common complication in Autosomal dominant polycystic kidney disease (ADPKD) patients. A few in vitro and in vivo studies showed that kidney and ureter stone formation could accelerate renal disease progression in ADPKD. However, its association between nephrolithiasis and renal function deterioration remains unknown in ADPKD patients. Methods: This single-center prospective cohort study, HOPE-PKD, analyzed 410 subjects who underwent abdominal CT scans within a year before enrollment. Subjects were divided into stone (n=80, 19.5%) and no-stone (n=330, 80.5%) groups based on CT findings. The primary outcome was the initiation of renal replacement therapy due to end-stage renal disease, and the secondary outcome was a composite of a 50% decline in eGFR, doubling of serum creatinine, or initiation of renal replacement therapy. Results: There was no statistical difference in baseline characteristics between the stone and no-stone cohorts. During a median 5.18 [interquartile range 3.41 - 8.03] year of follow-up, the primary and secondary outcomes occurred in 51 (12.4%) and 96 (23.4%) patients, respectively. In the unadjusted Cox regression analysis, there was no significant difference in the survival analysis between the two groups. However, after adjusting possible confounding factors (age, sex, body mass index, eGFR, comorbidity of hypertension and diabetes, serum uric acid, phosphorous, calcium level, results of PKD1 and PKD2 gene analysis, and Mayo classification), the stone group showed an increased risk of the primary and secondary outcome of HR 2.84 (95%CI 1.26 - 6.38; p-value 0.012) and HR 1.83 (95% CI 1.03 - 3.27; p-value 0.041), respectively compared to the no-stone group (Figure 1). Conclusion: This study demonstrates an association between nethrolithiasis and adverse renal outcome in ADPKD patients, underscoring the need for further clinical studies to enhance renal outcomes.Figure 1. Survival curve for primary outcome (A) and secondary outcome (B) obtained by means of multivariate Cox regression model, in model 4.